We have preliminary data, based on only about 1,000 mice, that susceptibility to tumor induction by Rous Sarcoma Virus is under multigenic control. One of the genes seems to be located within the H-2 complex and at least one other is elsewhere. We propose to extend this study, using congenic strains of mice produced within our own mouse colony for this purpose, in an attempt to define the nature and mechanism of this genetic control. This study will generate relatively large numbers of primary tumor bearing mice which will be utilized in the studies described below. The overall objective is to determine the biological significance of the various components of the immune response against primary tumors. The system chosen for study is that of primary sarcomas induced in inbred mice by neonatal injection of Rous Sarcoma Virus (RSV). Cell- mediated immunity (CMI), serum blocking factor (SBF) and unblocking factor (UBF) will be measured by the microcytotoxicity testing using established Rous sarcoma tissue culture cells as targets. These measurements will be made during the development and progress of primary tumors, in mice which were inoculated with RSV as newborns but which failed to develop tumors and in transplanted tumor hosts. These same animals will act as donors of lymphoid cells and/or serum for transfer to sublethally irradiated syngeneic recipients which will then be challenged with a standard dose of compatible Rous sarcoma. The influence of the transferred cells and/or serum on the growth of the challenge tumor will then be measured and an attempt made to correlate these biological effects with the measurements obtained in vitro.